Mylotarg (gemtuzumab ozogamicin), previously taken off the market, is shown in additional clinical studies to be effective for acute myeloid leukemia.

Pfizer has had success obtaining FDA approvals for antibody-drug conjugates (ADCs) recently. The latest approval is for Mylotarg (gemtuzumab ozogamicin) (https://connect.dcat.org/blogs/pharma-news/2017/09/05/pfizer-merck-co-teva-and-roche-lead-drug-approvals#.WbaBENGQzIU), an ADC for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), and adults and children two years and older with relapsed or refractory CD33-positive AML. MYLOTARG is the first therapy with an indication that includes pediatric AML, according to Pfizer. Earlier in August 2017 the company received approval for Besponsa (inotuzumab ozogamicin), an ADC for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.

AML is the most common type of acute leukemia in adults and the second most common leukemia in children and accounts for approximately 80% of all cases of acute leukemia. Sadly, only one in four patients with AML survives longer than five years. 

In MYLOTARG, the cytotoxic agent calicheamicin is linked to a monoclonal antibody (mAB) targeting CD33, an antigen expressed on the surface of myeloblasts in up to 90 percent of AML patients. According to Pfizer, when Mylotarg binds to CD33 antigens on cell surfaces, it is absorbed into the cells, resulting in the release of calicheamicin and cell death. 

The drug received its first FDA approval in 2000 under an accelerated approval program for use at a higher dose as a single treatment for first-relapse patients with CD33-positive AML who were 60 years or older. After results of a confirmatory phase 3 trial failed to show a clinical benefit but had a higher fatal induction toxicity rate than placebo, company voluntarily withdrew Mylotarg from the market in 2010. the reintroduction is “supported by continued research by the AML community demonstrating a favorable risk: benefit profile,” according to the company. “Due to the critical unmet need for patients with AML, there remained great interest among AML clinicians to evaluate MYLOTARG using different doses and different schedules. These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of MYLOTARG,” the company stated in a press release. 

The ADC was originally developed by Pfizer and Celltech (now UCB), but Pfizer has responsibility for all manufacturing, clinical development and commercialization activities. The drug is already available in Japan for the treatment of patients with relapsed or refractory CD33-positive AML who are not considered candidates for other cytotoxic chemotherapy.

“The FDA approval of MYLOTARG fills a critical unmet need for many adults and children with AML, which can be fatal in a matter of months or even weeks if not treated and has a high relapse rate,” said Liz Barrett, Global President, Pfizer Oncology. “Based on clinical data, real-world experience and support from the AML community, we are grateful MYLOTARG now has the potential to help a broad range of AML patients. 

“Today is an important day for patients, their families and the entire AML community, as the approval of MYLOTARG brings forth a long-awaited treatment option that may lead to deeper, more durable remissions for patients with AML,” said Jorge Cortes, MD, University of Texas, MD Anderson Cancer Center. “After many years, we are finally seeing progress in the treatment of AML, which has renewed my hope in improving outcomes for my patients. I am pleased that I can now offer many adult and pediatric patients targeted treatment with MYLOTARG.”